Networks of C-reactive protein and depression symptoms in patients with stable coronary heart disease: Findings from the Heart and Soul Study

Abstract

Objective: Research addressing the associations between C-reactive protein (CRP) and depression among patients with stable coronary heart disease (CHD) has produced inconsistent results. This might be attributable to varying associations of CRP with specific depression symptom profiles. We responded to this challenge using various network analysis techniques.

Methods: A total of 967 outpatients with documented CHD were drawn from the baseline cross-sectional data of the Heart and Soul Study. We first estimated mixed graphical models that included CRP and individual depression symptoms, before and after adjusting for relevant covariates, to explore whether CRP is correlated with specific facets of depression. We also investigated whether CRP levels moderated the associations between specific depression symptoms using moderated network models. Finally, we performed a network comparison test and compared the symptom network properties between non-elevated and elevated CRP groups.

Results: In the network model without covariates, CRP was positively associated with fatigue, appetite changes, and psychomotor problems. CRP maintained its negative association with concentration difficulty regardless of covariate adjustment. Few symptom-symptom associations, especially those involving appetite changes, were moderated by CRP. Further, the elevated CRP group showed greater overall symptom connectivity as compared to the non-elevated group.

Conclusion: This study segues into CRP-depression relationship with sophisticated methodology.

Keywords: C-reactive protein; coronary heart disease; depression; network analysis.

FIGURE 1

Network model of pairwise interactions with (a) and without adjustment for covariates (b). Green edges represent positive associations between the nodes and red edges represent negative edges between the nodes with thicker edges representing stronger association. Gray edges signify pairwise interactions wherein no sign is defined (i.e., interactions involving categorical variables). Alc, alcohol use; Antidepre, antidepressants use; App, appetite changes; BMI, body mass index; Conc, concentration difficulty; CRP, C‐reactive protein; Fati, fatigue; Fgn, fibrinogen; HDL, high density lipoprotein; Lost_int, loss of interest; Motor, psychomotor problems; Phys, physical activity; Sad, feelings of sadness; Slp, sleep disturbance; Worth, feelings of worthlessness; Smok, current smoking status; Suic, suicidal ideation; TG, triglycerides; WBC, white blood cell.

FIGURE 2

Moderated network models conditioned on CRP group (<3.0 mg/L, left panel; ≥3.0 mg/L, right panel). As CRP is the moderator being conditioned on in the network, there are no edges connected to CRP and it is simply included in the visualization of the models to indicate its role as the moderator. Green edges represent positive linear relations. App, appetite changes; Conc, concentration difficulty; CRP, C‐reactive protein; Fati, fatigue; Lost_int, loss of interest; Motor, psychomotor problems; Sad, feelings of sadness; Slp, sleep disturbance; Worth, feelings of worthlessness; Suic, suicidal ideatio.

FIGURE 3

Moderated network models conditioned on three CRP levels. Network is depicted at −1SD, mean, and +1SD of CRP level. As CRP is the moderator being conditioned on in the network, there are no edges connected to CRP and it is simply included in the visualization of the models to indicate its role as the moderator. Green edges represent positive linear relations. App, appetite changes; Conc, concentration difficulty; CRP, C‐reactive protein; Fati, fatigue; Lost_int, loss of interest; Motor, psychomotor problems; Sad, feelings of sadness; Slp, sleep disturbance; Suic, suicidal ideation; Worth, feelings of worthlessness.